title: The effects of isoflurane anesthesia and mechanical ventilation on renal function during endotoxemia.
abstract: BACKGROUND
  Isoflurane is a common anesthetic agent used in human surgery and in animal models of sepsis. It has been suggested to have beneficial anti-inflammatory properties and to protect kidney function. Here, we investigated the effect of isoflurane on the development of kidney injury and dysfunction during 48-h endotoxemia in sheep.
  
  
  METHODS
  Before the experiments, the sheep (n=16) were surgically equipped with transit-time flowprobes around the renal, femoral and superior mesenteric artery. The animals were randomized to either be anesthetized with isoflurane and mechanically ventilated or to remain conscious while they received intravenous Escherichia coli lipopolysaccharide (LPS) for 48 h (25 ng/kg/min). In two animals in each group, the LPS was excluded to investigate any effect of isoflurane per se over time.
  
  
  RESULTS
  Endotoxemia caused cardiovascular changes typical for hyperdynamic sepsis and, although renal hyperemia occurred, impaired renal function in both groups. Compared with conscious animals, isoflurane significantly (P<0.05) reduced urine output, renal creatinine clearance, fractional sodium excretion and renal blood flow during endotoxemia. Furthermore, the plasma concentrations of urea and creatinine increased more in the anesthetized animals. Isoflurane anesthesia also enhanced neutrophil activity and accumulation in the kidney during endotoxemia. N-acetyl-β-D-glucosaminidase was significantly increased, with no inter-group difference as an indication of tubular injury.
  
  
  CONCLUSIONS
  The results of the current study suggest that isoflurane anesthesia (minimum alveolar concentration 1.0) with mechanical ventilation aggravates renal dysfunction during 48 h of endotoxemia and does not significantly reduce the inflammatory response or signs of tubular damage.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. robert.frithiof@ki.se
authors.forename: R
authors.initials: R
authors.lastname: Frithiof
authors.forename: O
authors.initials: O
authors.lastname: Soehnlein
authors.forename: S
authors.initials: S
authors.lastname: Eriksson
authors.forename: J
authors.initials: J
authors.lastname: Fenhammar
authors.forename: H
authors.initials: H
authors.lastname: Hjelmqvist
authors.forename: L
authors.initials: L
authors.lastname: Lindbom
authors.forename: M
authors.initials: M
authors.lastname: Rundgren
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D054441:Cell Migration Assays, Leukocyte; D003404:Creatinine / Q000097:blood; D019446:Endotoxemia / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007677:Kidney Function Tests; D008070:Lipopolysaccharides / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D012121:Respiration, Artificial; D012756:Sheep; D014508:Urea / Q000097:blood; D014563:Urodynamics / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D008070:Lipopolysaccharides; D000804:Angiotensin II; D001127:Arginine Vasopressin; D014508:Urea; D003404:Creatinine; D007530:Isoflurane; D009195:Peroxidase